Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries

Abstract

Introduction: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed.

Discussion: The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure.

Conclusions: GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets.

Keywords: Global Accelerator for Paediatric Formulations; HIV; drug development; drug formulations; paediatric drugs; regulatory approval; tuberculosis; viral hepatitis.

Figure 1

The Global Accelerator for Paediatric Formulations (GAP‐f). The GAP‐f formalizes collaboration across sectors to ensure accelerated development and uptake of the most needed drugs and formulations for children. SRAs, stringent regulatory authorities; NRAs, national regulatory authorities (in high‐burden countries).

Figure 2

The GAP‐f represents an opportunity to address challenges in paediatric drug formulation development. Challenges are grouped around three areas: dependence on adult drug development, paediatric formulation requirements and paediatric ARV market. Progress to‐date in addressing these challenges is depicted along a funnel originating from precursor mechanisms and leading up to the GAP‐f collaborative model. Legal framework challenges are placed outside of the funnel because of the limited influence of the GAP‐f to directly address these. PK, pharmacokinetic; GAP‐f, Global Accelerator for Paediatric Formulations; ARV, antiretroviral.

Figure 3

Timeline for ABC/3TC development. It took almost 15 years after ABC and 3TC were first approved for use in children until enough generic versions of child‐friendly formulations were produced to make these drugs widely available to children in LMIC. ABC, abacavir; 3TC, lamivudine; LMIC, low‐ and middle‐income countries.